Glucocorticoid neuropharmacology will be extended as indicated by research initiated 3 years ago. Using cat neuromuscular and spinal segmental systems in vivo, intensive glucocorticoid dosing was found to enhance facilitation, excitability and transmission presynaptically. Selectivities of these effects will now be defined for phasic and tonic motor neurons. Therefore, motor nerve terminal (mnt) excitabilities, facilitatory and transmitter functions and neuronal impulse generating capacities will be compared. Motor nerve differences will aid understanding of trophism, glucocorticoid myopathies and therapeutic effectiveness in neurologic diseases. The recently described cAMP system of cat soleus mnt's will be examined as a basis of glucocorticoid action. New findings will be used to further understand demonstrated glucocorticoid effectiveness in preserving motor nerve function in two model neuropathies in cat. Ultrastructure correlates of glucocorticoid preservation of function will be sought. In the cat spinal segmental system, selectivity of glucocorticoid actions for excitatory vs. inhibitory paths will be determined. Intracellular, intramedullary and input-output methods will be used to distinguish pre- and post-junctional loci of action; effects on transmitter dynamics in the 2N system will be analyzed. Dose and time correlates of glucocorticoid effects require definition. Glucocorticoid contents in nervous tissues will be correlated with neuropharmacologic effects; uptake and loss will be defined for single and multiple dosing. Specificity of glucocorticoid action will be tested via SAR studies and via neurophysiologic deficits caused by adrenalectomy. Glucocorticoid type molecules, lacking hormonal activity, will be tested in normal and neuropathic systems. If the same presynaptic effects occur as with regular glucocorticoids, opportunity for selective drug development will be at hand. Conversely, specific corticosteroid control of certain presynaptic functions will be explored; nothing is known about this. Preliminary data indicate that cortisol regulates mnt function. Glucocorticoid effects on high affinity choline uptake by cat caudate synaptosomes will be examined to further understand glucocorticoid action on nerve terminals.